Following acute coronary occulsion, the coronary collateral circulation becomes the primary determinant of the extent of ischemia within the involved myocardium. Accordingly, the overall objective of the proposed research is to obtain a more complete understanding of the functional properties of the coronary collateral circulation and its development. Experiments will be carried out on the coronary circulation in dogs, pigs, rats, and in some cases, functional and anatomical measurements will be conducted in human hearts obtained at autopsy. Recent studies from this laboratory have shown that the coronary circulation acts as a functional end artery circulation in which the significant collateral vessels are inter-arterial anastomoses. Based on this view, a detailed model of the coronary collateral circulation is proposed and the experiments are designed to test the properties of the individual elements of this model. A wide variety of physiological measurements including myocardial blood flow with radioactive microsphere, retrograde coronary blood flow and pressures will be made in animals prepared for acute study under highly controlled conditions and in animals prepared with implanted occluders for study under chronic conditions. Anatomical studies will be carried out in parallel, including injection studies of the coronary and coronary collateral circulations and histological examination of the developing collateral circulation. Specific attention will be directed at the relationship between the distribution of the collateral circulation and the histological evidence of necrosis. It is hoped that a model will be developed which can confidently predict changes in collateral function based on only measurements that can be obtained in infarct patients. It will then be possible to evaluate clinical feasibility of interventions designed to protect ischemic myocardium and minimize infarct size in terms of the effect on coronary collateral blood flow.